Tramadol In Dogs Research Articles

Post-operative analgesia following TPLO surgery: A comparison between cimicoxib and tramadol

ObjectiveTo compare the analgesic effects of oral administration of cimicoxib and tramadol over a 30 day period following Tibial Plateau Leveling Osteotomy and partial menisectomy in dogs. DesignRandomized, double blinded, prospective clinical trial. Animals42 adult client-owned dogs with unilateral cranial cruciate ligament disease and partial meniscal tears. MethodsDogs were allocated into 2 treatment groups (cimicoxib or tramadol). Weight bearing while standing, thigh circumference, flexion and extension range of motions, wound classification, adverse effects, Visual Analogue Scale (VAS), Glasgow Composite Measure Pain Scale (CMPS-SF) and Helsinki Chronic Pain Index (HCPI) questionnaire and limb function by means of pressure platform gait analysis were recorded before surgery and at several time points after surgery for 30 days. Outcome measures were compared at each time point among groups. ResultsA significant improvement in two objective measures of gait of the cimicoxib group: the vertical impulse on day 1 and day 20 and the peak vertical force on day 20 were significantly improved when compared to the tramadol group. However, no difference was seen for the VI or PVF of dogs on the other days compared. In addiction there was no difference in the weight bearing while standing, thigh circumference, wound classification, adverse effects, VAS, CMPS-SF and HCPI. We did not observe a difference in the number of adverse effects measured in this study with the exception of hock edaema. Conclusions and clinical relevanceA significant difference was not found in long-term postoperative analgesia provided by cimicoxib or tramadol in dogs undergoing TPLO when subjective parameters (with the exception of knee joint range of motion) were evaluated, but use of the force plate analysis revealed a significant difference between groups at T20 for both PVF and VI. The use of cimicoxib improved the limb function and ROM and reduced the occurrence of hock edema, in the first 20 days after surgery, without any additional side effects, compared to tramadol. Thus, the use of cimicoxib should be preferred to tramadol alone in clinical cases similar to the ones included in this study.

Efficiency of Epidurally Injected lidocaine, lidocaine and Morphine or Lidocaine and Tramadol for Postoperative Analgesia in Dogs Following Orchiectomy and Ovariohysterectomy

The objective of this study was to evaluate and compare the postoperative analgesia provided by epidural lidocaine, lidocaine and morphine or lidocaine and tramadol in dogs following elective orchiectomy or ovariohysterectomy. Thirty-six clinically healthy dogs, classified as class I and II according to the American Society of Anesthesiologists classification system, were randomly allocated into three groups of 12 each, with six females and six males. The dogs received 4mg/kg of lidocaine combined with 0.01ml/kg of 0.9% NaCl, 0.1mg/kg of morphine or 1.0mg/kg of tramadol epidurally. Postoperative pain was assessed 4, 8, 12, 18 and 24 hours after epidural anaesthesia using the University of Melbourne pain scale (UMPS), by a single male observer who was blinded to the epidural protocol. According to the obtained results, evaluated epidural protocols provided sufficient and comparable postoperative analgesia throughout the complete 24-hours observation period. The appearance of vocalization or painful reaction to palpation of the wound surrounding tissue were absolutely absent. Values of 10 points, or higher, indicating the presence of moderate to severe pain and the necessity of additional analgesia, were not recorded. However, established quality of postoperative analgesia is probably not the sole result of epidural administration of drugs, but also analgesic activity of drugs used for general anaesthesia (xylazine and ketamine), and their mutual synergistic or additive effects.

Pharmacokinetics and analgesic efficacy of intranasal administration of tramadol in dogs after ovariohysterectomy

ObjectiveTo assess analgesic efficacy and the pharmacokinetics of intranasal (IN) tramadol in dogs following ovariohysterectomy. Study designRandomized, blinded clinical study. AnimalsA total of 30 bitches undergoing elective ovariohysterectomy. MethodsDogs were randomly assigned to one of three experimental groups (10 dogs per group): IN tramadol 4 mg kg–1 (group T-IN), intravenous (IV) tramadol 4 mg kg–1 (group T-IV) and IV methadone 0.2 mg kg–1 (group M). Drugs were administered at extubation. At established time points (before surgery and up to 8 hours after drug administration) analgesia was assessed using the Italian version of the Glasgow Composite Measure Pain Scale Short Form and physiological variables were recorded. To determine the pharmacokinetics of IN tramadol, blood samples were collected at predetermined time points. Shapiro–Wilk test was used to assess whether data were normally distributed and consequently parametric or non parametric tests were applied. A p value < 0.05 was considered significant. ResultsNo significant intergroup differences were observed in the dogs that were administered rescue analgesia and time of its administration. Excluding dogs that were administered rescue analgesia, no significant intergroup differences emerged in pain scores and physiological variables, except for a lower rectal temperature in group M compared with the tramadol groups. After IN administration, tramadol was rapidly absorbed into the systemic circulation, reaching its maximum concentration (range 74.74–200.29 ng mL–1) within 30–60 minutes, it then decreased rapidly and was detectable in plasma for up to 2 hours after treatment in all dogs. Conclusions and clinical relevanceIN tramadol administration appears to be as effective as IV tramadol and methadone treatments in pain management of dogs after elective ovariohysterectomy. Given its low concentrations and short detection time in plasma after the IN route, systemic tramadol action appears unlikely.

Comparison of sedative and some cardiopulmonary effects of intramuscular medetomidine or medetomidine–tramadol in dogs

ObjectiveTo evaluate the clinical and physiologic effects of intramuscular (IM) administration of medetomidine with and without tramadol in dogs. Study designProspective experimental study. AnimalsA group of eight mixed breed dogs of both sexes, aged 1–2 years, weighing 16.0 ± 0.6 kg. MethodsEach dog was studied twice at ≥1 week interval. Medetomidine (5 μg kg–1; treatment M) was administered IM alone or with tramadol (4 mg kg–1; treatment MT). Sedation was scored by a system that included vocalization, posture, appearance, interactive behaviors, resistance to restraint and response to noise. Times from drug administration to ataxia, impaired walking, head drop, sternal and lateral position and standing were recorded. Sedation score, heart rate, respiratory rate, rectal temperature, end-tidal carbon dioxide (Pe′CO2), hemoglobin oxygen saturation and mean noninvasive blood pressure were recorded and compared 15 minutes before and 15, 30 and 45 minutes after drug administration. ResultsDogs administered MT had higher sedation scores than dogs administered M at 30 and 45 minutes after drug administration (p < 0.05). Times to ataxia, impaired walking, head drop and sternal recumbency were not different between the treatments. Time to lateral recumbency was longer in M than in MT (21.1 ± 1.0 versus 17.6 ± 0.7 minutes, respectively; p < 0.05). Time to standing was longer in MT than in M (67.9 ± 1.4 versus 54.5 ± 1.9 minutes, respectively; p < 0.001). Measured physiological variables did not differ between the treatments, with the exception of Pe′CO2, which was higher in MT than in M at all post-treatment evaluation times (p < 0.001). Conclusions and clinical relevanceTramadol combined with medetomidine resulted in greater sedation scores (deeper sedation) than medetomidine alone in dogs, and minimal adverse changes in the physiologic variables were measured.

Safety and efficacy of reduced dosage ketoprofen with or without tramadol for long-term treatment of osteoarthritis in dogs: a randomized clinical trial

BackgroundThis study aimed to evaluate the safety and efficacy of reduced-dosage ketoprofen with or without tramadol in dogs. Five healthy dogs receiving standard-dosage ketoprofen (2 mg/kg SC, then 1 mg/kg PO daily) comprised Group A. Twenty dogs with osteoarthritis were randomized to receive reduced-dosage ketoprofen (0.5 mg/kg SC once; 0.25 mg/kg PO daily) alone (Group B) or in combination with tramadol (5 mg/kg/day PO) (Group C). Treatments were administered for 28 days. Platelet aggregation time (PAT), gastrointestinal (GI) endoscopy and glomerular filtration rate (GFR) were performed up to 60 days after treatment initiation. Pain was scored using a validated clinical metrology instrument up to D120. Data were analyzed with general linear mixed model for repeated measures (α = 0.05).ResultsPAT was not different between groups but was increased with time for all groups. GI lesion scores were higher in Group A than Groups B and C (day 28; P = 0.005) and were increased with time for Group A (P = 0.005). GFR was lower in Group A than Groups B and C (day 28; P < 0.01) and were decreased with time for group A (P < 0.001). Standard-dosage ketoprofen administration resulted in clinically relevant adverse effects. Pain score decreased in both treated groups (B and C) from D0 to D28. Need of rescue analgesia from D29 to D120 was higher in Group B than in Group C (P = 0.039).ConclusionsThe long-term safety profile of reduced-dosage ketoprofen is similar whether the drug is administered alone or in combination with tramadol to dogs with osteoarthritis. Analgesic efficacy of the combination looks attractive.

Identification of canine cytochrome P-450s (CYPs) metabolizing the tramadol (+)-M1 and (+)-M2 metabolites to the tramadol (+)-M5 metabolite in dog liver microsomes.

We previously showed that (+)-tramadol is metabolized in dog liver to (+)-M1 exclusively by CYP2D15 and to (+)-M2 by multiple CYPs, but primarily CYP2B11. However, (+)-M1 and (+)-M2 are further metabolized in dogs to (+)-M5, which is the major metabolite found in dog plasma and urine. In this study, we identified canine CYPs involved in metabolizing (+)-M1 and (+)-M2 using recombinant enzymes, untreated dog liver microsomes (DLMs), inhibitor-treated DLMs, and DLMs from CYP inducer-treated dogs. A canine P-glycoprotein expressing cell line was also used to evaluate whether (+)-tramadol, (+)-M1, (+)-M2, or (+)-M5 are substrates of canine P-glycoprotein, thereby limiting their distribution into the central nervous system. (+)-M5 was largely formed from (+)-M1 by recombinant CYP2C21 with minor contributions from CYP2C41 and CYP2B11. (+)-M5 formation in DLMs from (+)-M1 was potently inhibited by sulfaphenazole (CYP2C inhibitor) and chloramphenicol (CYP2B11 inhibitor) and was greatly increased in DLMs from phenobarbital-treated dogs. (+)-M5 was formed from (+)-M2 predominantly by CYP2D15. (+)-M5 formation from (+)-M1 in DLMs was potently inhibited by quinidine (CYP2D inhibitor) but had only a minor impact from all CYP inducers tested. Intrinsic clearance estimates showed over 50 times higher values for (+)-M5 formation from (+)-M2 compared with (+)-M1 in DLMs. This was largely attributed to the higher enzyme affinity (lower Km) for (+)-M2 compared with (+)-M1 as substrate. (+)-tramadol, (+)-M1, (+)-M2, or (+)-M5 were not p-glycoprotein substrates. This study provides a clearer picture of the role of individual CYPs in the complex metabolism of tramadol in dogs.

Comparison of the effects of nefopam and tramadol on postoperative analgesia in dogs undergoing ovariohysterectomy

Relieving perioperative pain can reduce postoperative suffering and improve recovery from anaesthesia in animals. The aim of this study was to compare the analgesic effects of nefopam and tramadol in dogs undergoing ovariohysterectomy. Twenty-four adult mixed-breed female dogs were randomly divided into three groups (n = 8) and received their respective treatments immediately after surgery: Group T (2 mg/kg tramadol, i.v.), Group C (1 mg/kg nefopam, i.v.) and Group D (2 mg/kg nefopam, i.v.). The heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR) and rectal temperature (RT) were measured and the level of analgesia was assessed using the Glasgow Composite Measure Pain Scale (CMPS-SF). The CMPS-SF was performed at least two days before premedication (baseline), every 2 h for the first 8 h (post-extubation), at 12 h and at 24 h. Results showed that the HR in all groups was significantly (P &amp;lt; 0.05) higher at 2 and 6 h than at baseline. The RR in Group T was significantly higher (P &amp;lt; 0.05) at 0 and 2 h than at baseline. Rescue analgesia (0.2 mg/kg morphine, i.v.) was provided if CMPS-SF pain scores greater than or equal to six. Four dogs required rescue analgesia: one dog in Group T at 2 h and three dogs in Group C at 2 and 6 h. No dogs in Group D required rescue analgesia. The CMPS-SF pain scores of dogs in Group C were significantly higher (P &amp;lt; 0.05) than those in Group T at 6, 8 and 12 h. The scores in Group D were significantly lower (P &amp;lt; 0.05) than those in Group C at 2, 4, 6, 8 and 12 h. The scores in Group D were significantly lower (P &amp;lt; 0.05) than those in Group T at 2 and 4 h. However, the scores in Group D were not significantly different compared with Group T. In conclusion, this study suggests that nefopam at 2 mg/kg i.v. produces better postoperative analgesia compared with tramadol at 2 mg/kg i.v. or nefopam at 1 mg/kg i.v. in dogs undergoing ovariohysterectomy.

Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy

To evaluate the pharmacokinetics of hydrocodone (delivered in combination with acetaminophen) and tramadol in dogs undergoing tibial plateau leveling osteotomy (TPLO). 50 client-owned dogs. Dogs were randomly assigned to receive tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) following TPLO with standard anesthetic and surgical protocols. Blood samples were collected for pharmacokinetic analysis of study drugs and their metabolites over an 8-hour period beginning after the second dose of the study medication. The terminal half-life, maximum serum concentration, and time to maximum serum concentration for tramadol following naïve pooled modeling were 1.56 hours, 155.6 ng/mL, and 3.90 hours, respectively. Serum concentrations of the tramadol metabolite O-desmethyltramadol (M1) were low. For hydrocodone, maximum serum concentration determined by naïve pooled modeling was 7.90 ng/mL, and time to maximum serum concentration was 3.47 hours. The terminal half-life for hydrocodone was 15.85 hours, but was likely influenced by delayed drug absorption in some dogs and may not have been a robust estimate. Serum concentrations of hydromorphone were low. The pharmacokinetics of tramadol and metabolites were similar to those in previous studies. Serum tramadol concentrations varied widely, and concentrations of the active M1 metabolite were low. Metabolism of hydrocodone to hydromorphone in dogs was poor. Further study is warranted to assess variables that affect metabolism and efficacy of these drugs in dogs.

Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation.

To compare analgesia provided by carprofen and tramadol in dogs after enucleation. Randomized, masked clinical trial. 43 dogs. Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for signs of pain at baseline (ie, before carprofen or tramadol administration) and at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥ 9 (maximum possible score of 20), there was a score ≥ 3 in any of 5 behavioral categories (highest score possible per category was 3 or 4), or the visual analog scale (VAS) score was ≥ 35 (maximum possible score of 100) combined with a palpation score > 0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. No differences were found in age, sex, or baseline pain scores between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21), compared with dogs receiving carprofen (1/22). Pain and VAS scores decreased linearly over time. No significant differences were found in pain or VAS scores between groups at any time point (dogs were excluded from analysis after rescue). Results of this study suggested that carprofen, with opioid premedication, may provide more effective postoperative analgesia than tramadol in dogs undergoing enucleation.

Cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs

ObjectiveTo evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs. Study designExperimental, blinded, randomized, crossover study. AnimalsSix mixed breed dogs (two males and four females) weighing 10 ± 4 kg. MethodsThe animals were randomly divided into four treatments: D (10 μg kg−1 of dexmedetomidine), DM (dexmedetomidine 10 μg kg−1 and methadone 0.5 mg kg−1); DMO (dexmedetomidine 10 μg kg−1 and morphine 0.5 mg kg−1), and DT (dexmedetomidine 10 μg kg−1 and tramadol 2 mg kg−1). The combinations were administered intramuscularly in all treatments. The variables evaluated were heart rate (HR), respiratory rate (fR), rectal temperature (RT), systolic arterial pressure (SAP), sedation scale and pedal withdrawal reflex. These variables were measured at T0 (immediately before the administration of the protocol) and every 15 minutes thereafter until T105. ResultsA decrease in HR and fR occurred in all the treatments compared with T0, but no significant difference was observed between the treatments. The RT decreased from T45 onward in all the treatments. The SAP did not show a difference between the treatments, but in the DT treatment, the SAP was lower at T30 and T45 compared with T0. The D treatment had lower scores of sedation at T15 to T75 compared with the other treatments, and the DMO and DM treatments showed higher scores at T60 and T75 compared with DT. Conclusions and clinical relevanceThe treatments with morphine and methadone added to the dexmedetomidine showed higher sedation scores than the control treatment and the treatment with tramadol added to the dexmedetomidine showed no relevant differences in any of the variables evaluated in the study.

Influence of Surgery on the Pharmacokinetics of Tramadol Following Intravenous Administration in Dogs

Surgery and anesthesia causes fluctuations in hemodynamics which can lead to subtherapeutic drug levels and usually therapeutic failure, making postsurgical pain management difficult. The influence of surgery and anesthesia on the pharmacokinetics of intravenous tramadol in dogs was investigated. Tramadol (3 mg kg-1) was administered during premedication to female dogs (n = 6) undergoing ovariohysterectomy (Group 1) and to another non-surgery group (n = 6) of female dogs (Group 2) and the pharmacokinetics were compared between the groups. The outcome of this study showed that surgery and anesthesia affected the pharmacokinetics of tramadol, as indicated by a two-fold increase in the elimination half-life (1.10±0.18 h in Group 1 compared to 0.49±0.07 h in Group 2) and a three-fold increase in the area under the curve (770.21±117.76 ng.h mL-1 for Group 1 compared to 117.61±85.16 ng.h mL-1 for Group 2). Clearance was also significantly lower (3.98±0.56 mL min-1 kg-1) in Group 1 than in Group 2 (21.06±9.34 mL kg-1). Serum levels of both interleukin-6 and β-endorphin were increased at 6 and 9 h in the surgery group which further indicates that the rapid metabolism and clearance of tramadol in dogs are correlated with postsurgical pain. Therefore, re-administration of tramadol at 3 h is necessary for pain control. This suggests that surgery has a significant effect on the pharmacokinetics of tramadol in dogs

Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy.

Effect of oral co-administration of frozen-dried grapefruit juice on pharmacokinetics of tramadol in dogs

Summary Tramadol is a centrally acting analgesic drug extensively metabolized in animal species. Its clinical response is mainly due to the M1 metabolite, poorly produced in dogs. Grapefruit-juice can inhibit the metabolism of different drugs in animals and humans. The aim of the present study was to evaluate the pharmacokinetics of tramadol and its major metabolites after co-administration of tramadol and frozen-dried grapefruit-juice. A balanced cross-over study was used involving six male Beagle dogs. They were administered with tramadol alone (5 mg/kg) or with tramadol (5 mg/kg) plus frozen-dried grapefruit-juice (10 g). The plasma concentration vs time curves showed significant differences during the first 4 h following drug administration. Tmax was at 1.33 and 1.70 h following tramadol and tramadol plus frozen-dried grapefruit-juice treatment, respectively. Significant differences were also shown in Cmax (490 vs 270 ng/ml) and AUC (11,610 vs 5,890 h·h·ng/ml). Significant differences between the treatments were shown in all the M1 parameters reported. M2 and M5 did not show significant differences after both administrations. In conclusion, the frozen-dried grapefruit-juice was shown to affect the plasma concentrations of M1, despite them being well below those reported in humans.

Cardiovascular Effects of Tramadol in Dogs Anesthetized with Sevoflurane

Cardiovascular effects of tramadol were evaluated in dogs anesthetized with sevoflurane. Six beagle dogs were anesthetized twice at 7 days interval. The minimum alveolar concentration (MAC) of sevoflurane was earlier determined in each dog. The dogs were then anesthetized with sevoflurane at 1.3 times of predetermined individual MAC and cardiovascular parameters were evaluated before (baseline) and after an intravenous injection of tramadol (4 mg/kg). The administration of tramadol produced a transient and mild increase in arterial blood pressure (ABP) (P=0.004) with prolonged increase in systemic vascular resistance (SVR) (P<0.0001). Compared with baseline value, mean ABP increased significantly at 5 min (119% of baseline value, P=0.003), 10 min (113%, P=0.027), and 15 min (111%, P=0.022). SVR also increased significantly at 5 min (128%, P<0.0001), 10 min (121%, P=0.026), 30 min (114%, P=0.025), 45 min (113%, P=0.025) and 60 min (112%, P=0.048). Plasma concentrations of tramadol were weakly correlated with the percentage changes in mean ABP (r=0.642, P<0.0001) and SVR (r=0.646, P<0.0001). There was no significant change in heart rate, cardiac output, cardiac index, stroke volume, pulmonary arterial pressure, right atrial pressure and pulmonary capillary wedge pressure. In conclusion, the administration of tramadol produces a prolonged peripheral vascular constriction in dogs anesthetized with sevoflurane, which is accompanied with a transient and mild increase in arterial blood pressure. It also indicated that the degree of vasoconstriction might depend on the plasma concentration of tramadol.

Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs

The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile. After capsules administration of tramadol (4 mg/kg), involving eight male Beagle dogs, the concentration of tramadol and its main metabolites, M1, M2 and M5, were determined in plasma and urine using an HPLC method. The plasma concentrations of tramadol and metabolites were fitted on the basis of mono- and non-compartmental models, respectively. Tramadol was detected in plasma from 5 min up to 10 h in lesser amounts than M5 and M2, detected at similar concentrations, while M1 was detected in negligible amounts. In the urine, M5 and M1 showed the highest and smallest amount, respectively; M1 and M5 resulted widely conjugate with glucuronic acid. In conclusion, after oral administration of tramadol immediate release capsules, the absorption of the active ingredient was rapid, but its rapid metabolism quickly transformed the parental drug to high levels of M5 and M2, showing an extensive elimination via the kidney. Hence, in the dog, the oral immediate release pharmaceutical formulation of tramadol would have different pharmacokinetic behaviour than in humans.

Pharmacokinetics of tramadol and its major metabolites following rectal and intravenous administration in dogs

AIM: To compare the rectal and I/V administration of tramadol in dogs, to assess both its pharmacokinetic properties and absolute bioavailability. METHODS: After rectal administration via suppositories and I/V injection of tramadol (4 mg/kg), the concentration of tramadol and its main metabolites, O-desmethyl-tramadol (M1), N-desmethyl-tramadol (M2) and N,O-didesmethyl-tramadol (M5), were determined in plasma, using high-performance liquid chromatography (HPLC). A balanced cross-over study was used, involving six male Beagle dogs. RESULTS: Plasma concentrations after rectal and I/V administration were fitted on the basis of mono- and bi-compartmental models, respectively. Following rectal administration tramadol was detected from 5 minutes up to 10 hours, in lesser amounts than M5 and M2, while M1 was detected in negligible amounts. Following I/V administration tramadol was detected up to 10 hours, M2 and M5 were detected at similar concentrations, and M1 was present at low concentrations. The area under the curve (AUC) of the three metabolites did not differ significantly after either route of administration of tramadol. The absolute bioavailability of tramadol via rectal administration was 10 (SD 4)%. CONCLUSIONS: After rectal administration of tramadol suppositories, absorption of the active ingredient was rapid, but its metabolism quickly transformed the parent drug to high levels of M2 and M5. CLINICAL RELEVANCE: In the dog, rectal pharmaceutical formulation of tramadol would have a different pharmacokinetic behaviour than in humans.

Pharmacokinetics and efficacy of intravenous and extradural tramadol in dogs

Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. The clinical efficacy and pharmacokinetic profile of intravenous (i.v.) and extradural (e.d.) tramadol (2 mg/kg) and its o-desmethyl metabolite were studied in dogs undergoing tibial plateau levelling osteotomy (TPLO). Intra-operative cardiorespiratory variables were monitored and post-operative pain was assessed using the short form of the Glasgow Composite Pain Scale. A rapid (<5 min) and effective production of o-desmethyl tramadol was recorded. The pharmacokinetic profile was similar for tramadol and its metabolite irrespective of the route of administration. E.d. tramadol provided sufficient intra- and post-operative analgesia without significant clinical side-effects, but the post-operative analgesia was comparable to that following i.v. administration and the e.d. route could therefore not be considered a practical alternative to the i.v. route.

Cardiorespiratory variables, bispectral index and recovery of anesthesia in dogs anesthetized with isoflurane, treated or not with tramadol

It was studied fortuitous cardiorespiratory and bispectral index changes in dogs anesthetized with isoflurane associated or not to tramadol. Sixteen dogswere distributed in two groups named CG (control group) and TG (tramadol group). General anesthesia was induced in all animals with isoflurane via mask. After 10 minutes, the animals of CG received 0.05ml/kg of saline solution at 0.9%, and TG received 2mg/kg of tramadol, both via intramuscular. It was evaluated heart rate, systolic, diastolic and mean arterial pressures; electrocardiography; respiratory rate; oxihemoglobin saturation; end tidal carbon dioxide; bispectral index and recovery of anesthesia. The administration of tramadol in dogs anesthetized with isoflurane did not produce changes in cardiorespiratory variables, bispectral index and anesthetic recovery time. In addition, this association promoted good quality of anesthetic recovery.